TY - JOUR
T1 - Immunotherapy for GRIN2A and GRIN2D-related epileptic encephalopathy
AU - Hausman-Kedem, Moran
AU - Menascu, Shay
AU - Greenstein, Yoram
AU - Fattal-Valevski, Aviva
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/7
Y1 - 2020/7
N2 - Background: GRIN-related developmental-epileptic encephalopathies are associated with a spectrum of neurodevelopmental disorders, including intellectual disability, epilepsy including continuous spike-and-wave during sleep syndrome (CSWS), or epilepsy-aphasia spectrum phenotypes such as in Landau-Kleffner syndrome. Efficacy of IVIG treatment was recently reported in a patient with LKS related to GRIN2A mutation. Aim and Methods: We describe the efficacy of Immunotherapy in 5 consecutive patients (4 males, age range 6 months-13 years) with molecularly confirmed GRIN-related epileptic encephalopathy (4 with GRIN2A- related epilepsy-aphasia spectrum/epileptic encephalopathy with CSWS, accompanied by verbal, communicative and behavioural regression, and one patient with GRIN2D – related infantile developmental-epileptic encephalopathy). All patients had global developmental delay/ intellectual disability in various degrees, and were resistant to anticonvulsants, but none of the patients had frequent clinical seizures. All patients received monthly infusion of IVIG 2 g/ kg for 6 months; 2 patients were also treated with high-dose corticosteroids. Results: Normalization or near normalization of the EEG was noted in 3 patients, from whom 2 had mild improvement in verbal abilities and communication skills. Perceptual/spatial abilities, as well as executive functions and attention span, remained significantly impaired. Conclusion: according to this preliminary, open-label study, Immunotherapy may lead to a clinical and electrographic improvement in patients with GRIN-related developmental-epileptic encephalopathies. Further studies to validate the efficacy of immunotherapy and the potential role of autoimmunity in GRIN-related disorders are needed.
AB - Background: GRIN-related developmental-epileptic encephalopathies are associated with a spectrum of neurodevelopmental disorders, including intellectual disability, epilepsy including continuous spike-and-wave during sleep syndrome (CSWS), or epilepsy-aphasia spectrum phenotypes such as in Landau-Kleffner syndrome. Efficacy of IVIG treatment was recently reported in a patient with LKS related to GRIN2A mutation. Aim and Methods: We describe the efficacy of Immunotherapy in 5 consecutive patients (4 males, age range 6 months-13 years) with molecularly confirmed GRIN-related epileptic encephalopathy (4 with GRIN2A- related epilepsy-aphasia spectrum/epileptic encephalopathy with CSWS, accompanied by verbal, communicative and behavioural regression, and one patient with GRIN2D – related infantile developmental-epileptic encephalopathy). All patients had global developmental delay/ intellectual disability in various degrees, and were resistant to anticonvulsants, but none of the patients had frequent clinical seizures. All patients received monthly infusion of IVIG 2 g/ kg for 6 months; 2 patients were also treated with high-dose corticosteroids. Results: Normalization or near normalization of the EEG was noted in 3 patients, from whom 2 had mild improvement in verbal abilities and communication skills. Perceptual/spatial abilities, as well as executive functions and attention span, remained significantly impaired. Conclusion: according to this preliminary, open-label study, Immunotherapy may lead to a clinical and electrographic improvement in patients with GRIN-related developmental-epileptic encephalopathies. Further studies to validate the efficacy of immunotherapy and the potential role of autoimmunity in GRIN-related disorders are needed.
KW - Developmental epileptic encephalopathy
KW - Epilepsy-Aphasia spectrum
KW - Epileptic encephalopathy
KW - Epileptic encephalopathy with continuous spike-and-wave during sleep syndrome
KW - GRIN2A
KW - GRIN2D
KW - IVIG
KW - Landau-Kleffner
UR - http://www.scopus.com/inward/record.url?scp=85082927496&partnerID=8YFLogxK
U2 - 10.1016/j.eplepsyres.2020.106325
DO - 10.1016/j.eplepsyres.2020.106325
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C2 - 32289570
AN - SCOPUS:85082927496
SN - 0920-1211
VL - 163
JO - Epilepsy Research
JF - Epilepsy Research
M1 - 106325
ER -